1. Field of the Invention
The present invention relates to an apparatus for determining the concentration of an analyte in a fluid medium. More particularly, the invention relates to a capacitive sensor which is uniquely designed to detect a change in the dielectric properties caused by biospecific binding of an analyte with a biochemical binding system. The biochemical binding system is selected to have specific affinity to the particular analyte or group of analytes under test.
2. Description of the Prior Art
Various prior art techniques have attempted to measure the concentration of an analyte in a fluid medium using a binding substance having specific affinity for the analyte. Immunoassays are used to identify analytes, such as haptens, antigens and antibodies in a fluid medium. These immunoassays are based on biospecific binding between components of a reaction pair, such as the biospecific binding between an antigen and an antibody. Tagging one of the components of the binding pair enables more detailed quantification. For example, radioimmunoassay uses a radioisotope as a label for one of the components of the biospecific binding pair. Similarly, fluorescent labels have been used with fluorescent immunoassay.
More recently, attempts have been made to develop an electrochemical sensor which can directly measure analyte concentration. Such sensors would greatly simplify and speed up immunoassay laboratory procedures and provide greater accuracy. These sensors generally detect a change in the physical, electrical or optical properties as one of the binding pairs (generally an antibody) biospecifically binds to its mate pair (generally an antigen). U.S. Pat. No. 4,314,821, issued to Thomas K. Rice detects the change in resonance frequency of a piezoelectric oscillator as antibodies bind to the oscillator. The change in resonant frequency is proportional to the build-up of bound complexes on the oscillator surface (i.e., the build-up of the antibody-antigen complex physically changes the resonance of the oscillator). In U.S. Pat. No. 4,238,757, issued to John F. Schenck, an antigen in a fluid medium is brought into contact with a protein surface layer and alters the charge of the surface layer through an antigen-antibody biospecific binding reaction. A field effect transistor is used to detect this change in charge. Similarly, U.S. Pat. Nos. 4,444,892 and 4,334,880 detects a change in charge which occurs with certain biospecific binding reactions by using a polyacetylene semiconductive device.
U.S. Pat. No. 4,219,335, issued to Richard C. Ebersole, teaches the use of immune reagents labeled with reactance tags. These tags can be detected electrically since they alter the dielectric, conductive or magnetic properties of the test surface. The patent teaches binding a receptor agent to a test surface. The patient's body fluid containing a certain antibody is added to the test area and the antibody complexes with the receptor agents. In a second step, the test area is exposed to a second immune reagent that is bonded to a reactance tag. This immune tag complexes with the receptor agent-patient antibody complex, if present, on the test surface. The reactance tag containing a metal or metal-oxide is then detected by electrical means.
U.S. Pat. No. 4,054,646, issued to Ivar Giaever, teaches a method for determining, by electrical means, whether an antigen-antibody reaction produces a monomolecular layer or a bimolecular layer. An antigen is used to coat a metal substrate. The coated substrate is then brought into contact with the fluid suspected to contain a certain antibody. If the antibody is present it adheres to the antigen layer forming a bimolecular layer. If the antibody is not present, a monomolecular layer remains. The next step is to place a mercury drop on the upper layer and measure the capacitance between the mercury drop and the metal substrate. Since the distance between the mercury drop and the metal substrate changes for the bimolecular layer as compared to the monomolecular layer, the measured capacitance also changes. U.S. Pat. No. 4,072,576, issued to Hans Arwin et al, teaches measuring the alternating voltage impedance between two platinum electrode plates immersed in a fluid medium. A biochemical substance, is adsorbed onto the metallic surface. If the fluid under test contains an analyte biospecific to the adsorbed substance binding will occur. For example, an antigen may be absorbed directly on the metal electrodes and a specific antibody in the test fluid may bind to it forming a complex which remains on the surface of the metal electrodes. The capacitance changes depending on whether the surface is coated with a monolayer of the antigen or whether a bimolecular layer, composed of antigen and antibody layers, are adsorbed onto the surface.